The Mouse Core is designed to provide animal breeding, maintenance, and phenotyping resources for program research projects and cores with a focus on the WRN gene, genomic instability and tumorigenesis. This core addresses the animal needs of the program project in a way as to increase the efficiency of animal use. Two common themes are prevalent: 1) the generation and use of genetically altered mice, and 2) the use of whole animal assays to help characterize features of tumor development and other related phenotypes. Specific aim 1 will generate new ES cell and 'knock-in' mouse models of WRN missense mutations and determine their cellular and organismal phenotypes. This core will provide the transgenic technology, resources and expertise to generate new lines of mice. All of the resources are in place to make targeting vectors, target mouse ES cells, generate chimeras and mutant mice, and genotype offspring to identify permanent founders. Specific aim 2 will maintain breeding colonies for new and established lines of mice. It is essential that the integrity of the genetic alteration of a specific line be maintained over several generations of back-crossing using sound breeding practices and accurate record keeping. In addition, basic observational assessments will be performed at the colony level to detect any unusual characteristics of newly generated mouse lines. Specific Aim 3 will conduct longitudinal studies on experimental cohorts of genetically defined mice. Phenotypic changes will be monitored and assessed in mice involved in project experiments. A systematic approach is necessary to detect phenotypic differences not easily discernible by casual observations. This core will provide mouse imaging resources as part of the phenotyping procedure. The need for an animal core is paramount in that all projects use mice. Consolidation of animal resources focused on maximizing efficiency and minimizing costs is essential to the success of this program project.